Canadian clinic first to offer controversial new form of IVF

Dr. Robert Casper, medical director of the Toronto Centre for Advanced Reproductive Technology, says the AUGMENT in-vitro fertilization (IVF) process, developed by Massachusetts-based OvaScience, could help couples that have previously struggled with IVF because of poor egg quality. Photo: Toronto Centre for Advanced Reproductive Technology

A Canadian fertility clinic has become the first in North America to offer women a way to add new life to old eggs, extending her child-bearing years and stirring fresh controversy in the largely unregulated world of assisted baby making.

The technique involves rejuvenating a woman’s mature eggs using healthy, young, energy-producing cells harvested from tiny pieces of tissue taken from the outer edges of her own ovaries.

The pricey procedure, called AUGMENT, is aimed at women with “compromised” egg health who long to carry their own biological babies and who don’t want to use eggs from younger donors.

TCART’s medical director, Dr. Robert Casper, says the treatment could help couples that have struggled through failed cycles of in-vitro fertilization (IVF) because of poor egg quality.

Younger women can have poor quality eggs because of inherited reproductive disorders, environmental factors or other medical conditions.

A scientist works on a nonviable embryo in this file photo. (Richard Drew/ Associated Press) []

But the new procedure, developed by Massachusetts-based OvaScience, is also being marketed to the wave of women postponing child-bearing only to discover their own eggs have effectively expired.

“The median age in our clinic last year was 39, which makes half the women we saw for the first time last year over 40,” said Casper, a professor of obstetrics and gynecology at the University of Toronto.

“The problem with waiting a bit is that the eggs have been there since you were born,” he said. “It’s like a flashlight that’s been sitting on a shelf in a closet for 35 years — the flashlight itself is OK, but the battery has rundown.

“And that’s what AUGMENT is doing: replacing the batteries.”

The clinic has achieved several pregnancies so far, including one 30-year-old woman now 10 weeks pregnant with twins.

Experts in ovarian physiology are watching closely.

“I think all of us that live in the ovary science world are really anxious to see what they’ve done,” said Dr. Roger Pierson, a professor of obstetrics and gynecology at the University of Saskatchewan.

You’re innovating in an area where the burden of a bad outcome goes on for a lifetime and the person bearing the highest cost can’t consent

Others say that, with scant published data to go on, too little is known about the potential risks — including to the babies.

“You’re innovating in an area where the burden of a bad outcome goes on for a lifetime and the person bearing the highest cost can’t consent,” noted American bioethicist Arthur Caplan told the Canadian Medical Association Journal in a recently published article about AUGMENT.

By the time a woman reaches her late 30s, the quality of her eggs begins an irreversible slide.

Eggs have 46 chromosomes to begin with, but they undergo a change when a woman ovulates. Each egg discards 23 of its chromosomes and, if it’s fertilized, takes in 23 from the sperm cell to replace them. That process requires a lot of energy.

In vitro fertilization funding has become an increasingly public discussion over the past few years. Now, a new form seeks to improve an older woman’s eggs instead of relying on luck or a donor. [REUTERS/Kacper Pempel]

The energy in eggs, and essentially in all human cells, is produced by mitochondria, little power packs that weaken with age. If there isn’t enough energy to separate the chromosomes properly, some get left behind, resulting in chromosomal abnormalities such as Down syndrome.

The idea behind AUGMENT is to boost the energy in older eggs by adding younger mitochondria harvested from egg-making stem cells, or precursor cells, that scientists only recently discovered exist in the lining of adult ovaries.

One of those scientists, Jonathan Tilly, is a co-founder of OvaScience.

It’s not yet clear what effect adding younger mitochondria to older eggs could have on babies

Pierson, of the University of Saskatchewan, said it’s not yet clear what effect, if any, adding younger mitochondria to older eggs could have on AUGMENT-conceived babies.

However, he believes it’s safer than controversial experiments conducted in the early 2000s, when U.S. researchers transferred mitochondria from a younger woman’s eggs into the eggs of older women, effectively creating babies born with genetic material from three people, including a second “mother.”

The experiments were roundly criticized as a threat to human heredity. But they resulted in the births of 58 babies “who appear to be fine,” OvaScience spokeswoman Theresa McNeely said in an email to Postmedia News.

McNeely said published studies involving mitochondrial transfer in animals and humans also show the procedure is safe and can increase the likelihood of fertilization and healthy, live births.
With IVF alone, success rates for older women are dismal: In Canada, the live birth rate per cycle of IVF started is about 10 per cent for women 40 and older. McNeely said OvaScience doesn’t have live birth rates for AUGMENT yet, but that the information is being collected for an international patient registry.

AUGMENT also uses a woman’s own mitochondria — not mitochondria from another woman, and because the material comes from the woman’s own body and isn’t manipulated, the procedure falls under Health Canada guidelines for “cell therapy,” Casper said, meaning the company doesn’t have to apply for a new drug submission.

The U.S. Food and Drug Administration believes otherwise: In 2013, OvaScience voluntarily halted enrolling women in U.S. trials after the FDA demanded it file an “investigational new drug” application. TCART in Toronto is one of only four reproductive centres in the world currently offering AUGMENT. The others are in the United Kingdom, the United Arab Emirates and Turkey.

“I would assume that if the embryos survive and you get a fetus implanted and growing that it shouldn’t be any different from a natural pregnancy,” he said. “I don’t think it’s very risky at all.”
Today, embryos created via IVF are often grown to the so-called “blastocyst” stage — five-days after fertilization — before being transferred to the woman’s uterus. But if a woman has poor-quality eggs, the embryos will often “arrest” before the fifth day, Casper said. “They don’t make it.”

With AUGMENT, three small pieces of ovarian tissue are taken during a laparoscopic biopsy. The tissue is frozen within an hour of collection, then thawed and specially processed to isolate the mitochondria.

A month after the biopsy, the woman undergoes a full IVF stimulation. The woman is given drugs to stimulate her ovaries to churn out multiple eggs. The eggs are retrieved from her ovaries, and then the mitochondrial preparation is injected along with her partner’s sperm into the eggs.

“The idea is to put back a few thousand mitochondria that hopefully will divide and repopulate the egg with healthy young mitochondria,” Casper said.

“We’ve had a few pregnancies already in the first 14 completed embryo transfers,” he added. All the pregnancies have been in women under 40 so far. Among the next 30 patients, “there will be a number of women (aged) 42, 43, and maybe even 45,” Casper said.

“I think it would be fantastic if it works for older women, because we really don’t have much to offer them,” he said.

A Toronto woman says she tried AUGMENT as her sixth try at IVF and is now pregnant, healthy and happy. (File photo) []

AUGMENT will cost about $25,000, on top of the cost of IVF, which usually runs about $12,000.

For one 30-year-old Toronto woman, AUGMENT was her sixth attempt at IVF.

“I have poor egg quality and I was a poor responder to medication — I would only get one or two eggs at the end and they wouldn’t fertilize,” said the woman, who asked not to be identified for reasons of privacy. She estimates she and her husband have spent $55,000 to $60,000 on failed fertility treatments over the past five years.

“It’s really intense, it’s really isolating and it takes a toll on your marriage and your friendships,” she said. “We were at the point where we had given up, and then this new treatment came about. It was a new chance for us.”

She became pregnant in early December, after one cycle of IVF with AUGMENT.

“I feel great. The pregnancy is going well,” she said. “I just feel very fortunate to have been part of this.”